Cleavage of alkyl o-hydroxyphenyl ethers



United States Patent 3,256,336 CLEAVAGE 0F ALKYL O-HYDROXYPHENYL ETHERS Robert G. Lange, Aifton, Mo., assignor to Monsanto Company, a corporation of Delaware No Drawing. Filed June 21, 1961, Ser. No. 118,514 17 Claims. (Cl. 26tl592) This invention relates to a process for the cleavage of alkyl o-hydroxyphenyl ethers. More particularly, the invention is concerned with the cleavage of alkyl o-hydroxyphenyl ethers in the presence of a tertiary amine and aluminum chloride.

The action of conventional cleavage reagents such as hydrogen chloride, hydrogen bromide, hydrogen iodide, dimethylamine hydrochloride, ethanolamine hydrochloride, pyridine hydrochloride, aluminum chloride, zinc chloride, and the like, under vigorous reaction conditions l00 C.), on alkyl o-hydroxyphenyl ethers results in highly-colored products containing much tar and/ or unreacted alkyl o-hydroxyphenyl ether. Such products are generally obtained in low yields and are difiicult to purify.

It is therefore a primary object of this invention to provide a new and improved method of cleaving alkyl 0- hydroxyphenyl ether compounds.

It is a further object of the invention to provide such a method wherein mild reaction conditions are used and wherein a pure product can be readily isolated in good yield.

Other and different objects, advantages and features of this invention will become apparent to those skilled in the art upon consideration of the following description thereof and the examples attendant thereto.

It has been found that the process of this invention can be employed with alkyl o-hydroxyphenyl ethers of the formula where R represents an alkyl radical of from 1 to 4 carbon atoms, R representsa member of the groupconsisting of hydrogen, halogen, alkyl and alkenyl radicals of from 1 to 4 carbon atoms and alkoxy radicals of from 1 to 4 carbon atoms, R" represents a member of the group consisting of halogen, nitro, sulfomethyl, sulfinomethyl, mercaptomethyl, sulfenomethyl, hydroxyl, hydrocarbons of from 1 to 18 carbon atoms and oxygenated hydrocarbons of from 1 to 18 carbon atoms, and n represents an integer from 0 to 3. The alkyl o-hydroxyphenyl ethers of this formula can be cleaved by reaction with a tertiary amine and anhydrous aluminum chloride in the presence of an inert organic solvent. The intermediate product which is formed is then hydrolyzed with aqueous acid to yield a product of the formula (Rm W wherein R, R and n have the same meaning as above.

As employed in this application, the term halogen includes chlorine, bromine, iodine and fluorine. As employed in this application, the term hydrocarbon includes both the aliphatic and aromatic radicals consisting solely of carbon and hydrogen. Illustrative of such hydrocarbons are methyl, ethyl, propyl, isopropyl, n-butyl,

Patented June 14, 1966 isobutyl, sec.-butyl, tert.-butyl, n-amyl, isoamyl, n-hexyl, isohexyl, heptyl, Z-ethylhexyl, octyl, isooctyl, Z-ethylheptyl, isononyl, decyl, isodecyl, dodecyl, tridecyl, tetradecyl, pentadecyl, octadecyl, cyclobutyl, cyclopentyl, 2- methylcyclopentyl, 3-methylcyclopentyl, 2,4-dimethylcyclopentyl, cyclohexyl, 3,5-dimethylcyclohexyl, cyclohexylmethyl, cyclohexylpropyl, methylcyclohexylethyl, 2-propylcyclohexyl, 3-dodecylcyclohexyl, cycloheptyl, 2,4-dimethylcycloheptyl, 2,3,S-trimethylcycloheptyl, naphthenyl, hydroabietyl, vinyl, allyl, methallyl, propenyl, isopropenyl, l-butenyl, 2-butenyl, 3-butenyl, pentenyl, hexenyl, heptenyl, octenyl, nonenyl, deceny-l, dodecenyl, cyclopentenyl, cyclohexenyl, propargyl, butynyl, octynyl, benzyl, 4-methylbenz'yl, 3-caprylbenzyl, phenylethyl, phenylpropyl, phenyldodecyl, phenyl, tolyl, xylyl, cumyl, cymyl, naphthyl, ethylphenyl, xenyl, vinylphenyl, allylphenyl and the like.

As employed in this application, the phrase oxygenated hydrocarbon includes not only those radicals wherein a hydrocarbon contains a terminal oxygen atom having a free valence thereon, but also other and different radicals consisting solely of carbon, hydrogen and oxygen wherein the latter forms part of a carbonyl, hydroxyl or alkoxy group. Illustrative of such oxygenated hydrocarbon radicals are methoxy, ethoxy, propoxy, butoxy, pentoxy, octoxy, decoxy, tetradecoxy, hexadecoxy, octadecoxy, cyclo-propoxy, cyclobutoxy, cyclohexoxy, methyl cyclopentoxy, cyclohexyl methoxy, cyclohexyl propoxy, cycloheptoxy, 3-dodecyl cyclohexoxy, phenoxy, naphthoxy, 3- phenylpropoxy, benzyloxy, Z-phenylethoxy, phenyldecoxy, ethyl phenoxy, toloxy, formyl, carboxy, hydroxyrnethyl, acetyl, acetoxy, allyloxy, benzoyl, 2,4-dihydroxyphenyl and the like. I

As can be seen from preceding illustrations, the substituents represented by R encompass a very extensive group of radicals. However, the moieties which occupy the meta positions and the para position, in respect to the ortho hydroxy group of the alkyl o-hydroxyphenol ether, have not been found to interfere with the desired ether cleavage in any way. The diverse nature of such moieties, particularly in the case of the oxygenated hydrocarbons, will be further exemplified below.

Among the alkyl o-hydroxyphenyl ethers which can be cleaved in accordance with this invention are guaiacol, vanillin, isovanillin, acetovanillone, 3-ethoxy-4-hydroxybenzaldehyde, ferualdehyde, syringaldehyde, vanilloyl acetyl, eugenol, chavibetol, isoeugenol, o-eugenol, o-isoeugenol, isochavibetol, ferulic acid, isoferulic acid, hydroferulic acid, hydroisoferulic acid, hydroxyferulic acid, vanillic acid, isovanillic acid, homovanillic acid, 4-npropyl guaiacol, S-iodoguaiacol, S-bromovanillim-Z-nitrovanillin, 6-nitrovanillin, coniferyl alcohol, vanillyl alcohol, vanillyl sulfinic acid, vanillyl amine, vanillyl mercaptan, 4- hydroxy-3-methoxy-5-methylphenyl propane, 4-hydroxy- 3-methoxytoluene-w-sulfonic acid, 3,6-dihydroxy-2,4-dimethoxybenzaldehyde, 2-ethoxy-l-(4-hydroxy-3-methoxyphenyl) -l -propane, 1- (4-hydroxy-3-methoxyphenyl -1 ,2- propanedione, l-ethoxy-1-(4-hydroxy-3-methoxyphenyl)- 2-propanone, 1-(4-hydroxy-3-methoxyphenyl) 2- propanone, 4-hydroxy-3-methoxy-n propylbenzene, 4,4 dihydroxy-3,3-dimethoxystilbene, vanillil, vanilloin, guaiacylacetone, 2,3-dihydroxy-3 guaiacylpropene 1,3,4',5'- trimethoxydiphenylmethane, 4-hydroxy 3 methoxytoluene, 2,4,4-trihydroxy-3-methoxy-5-propenylchalcone, 4- hydroxy-3-methoxy ethylbenzyl alcohol, u-guaiacylglycerol and the like.

It should be noted that the cleavage process of this invention is not applicable to ethers which do not conform to the structural formula set forth above. ample, such ethers as veratraldehyde, 3,4-diethoxybenzaldehyde, resorcinol monomethyl ether, m-methoxybenzaldehyde and anisole remain virtually unchanged in the pres- For ex- 7 ence of the reagents of this invention. It should also be noted that even alkyl o-hydroxyphenyl ethers remain virtually unchanged when the other ortho position contains a substituent outside the scope of R. An example of such a situation is the case of orthovanillin.

Various procedures can be employed in charging of the reactants in the process of this invention. The first pro-- cedure consists of slow addition of anhydrous aluminum chloride to the amine while cooling and stirring, followed by addition of the ether and then the solvent. However, this method is somewhat inconvenient since it produces a viscous slurry before addition of the solvent.

Another procedure involves preforming an aminealuminum chloride complex by adding the amine slowly and with cooling to anhydrous aluminum chloride slurried in a solvent such as pentane. The pentane is distilled off and the remaining solid is added to the ether and the solvent.

A preferred procedure comprises adding a solution of an ether in a solvent to anhydrous aluminum chloride to form a stirrable slurry. The amine is then added slowly and with cooling to complete the charge of reactants. This last procedure has the particular advantage of permitting close control of the temperature during the complex formation because addition of liquids at a uniform rate is much easier than addition of solids and, also, the time required for complex formation is reduced due to dilution of the reactants with the solvent..

Among the tertiary amines which can be used in the present process are the heterocylic tertiary amines such as pyridine, a-picoline, 'y-picoline, fl-picoline, quinoline, isoquinoline, 2-methyl quinoline, 3-methyl quinoline, 4-methyl quinoline, S-methyl quinoline, 6-methyl quinoline, 7- methyl quinoline, 8-methyl quinoline, Z-ethyl quinoline, 4- ethyl quinoline, 2,3-dimethyl quinoline, 2,4-dimethyl quinoline, 2,8-dimethyl quinoline, 3,4-dimethyl quinoline, 4,6-

-dimethyl quinoline, 4,7-dimethyl quinoline, 4,8-dimethyl quinoline, 5,8-dimethyl quinoline, 6,8-dimethyl quinoline,

2,3,8-trirnethyl quinoline, 2,4,8-trimethyl quinoline, 2-

methyl--ethyl pyridine, pyrimidine, 2,3-dimethyl pyridine, 2,4-dimethyl pyridine, 2,5-dimethyl pyridine, 2,6-dimethyl pyridine, 3,4-dimethyl pyridine, 3,5-dimethyl pyridine, 2- ethyl pyridine, 3-ethyl pyridine, 4-ethyl pyridine, 2,4,6- trimethyl pyridine, Z-propyl pyridine; the aromatic tertiary amines such as N,N-dimethylaniline, N,N-diethylaniline, and the like; and the aliphatic tertiary amines such as trimethylamine, trie'thylamine, tri-n-propylamine, triisopropylamine, tri-n-butylamine, triisobutylamine, tri-tert.-butylamine, triisoamylamine, tri-n-amylamine, trihexylamine, diethylmethylamine, dimethylethylamine, dimethylcyclohexylamine, dimethylhexylamine, diethylhexylamine, dimethyldecylamine and the like. It will be recognized that, besides containing nitrogen, the above-listed tertiary amines contain only hydrogen and carbon, whereby they may be described as tertiary hydrocarbyl amines.

The anhydrous aluminum chloride used in the process of this invention can be prepared by any of a number of methods well known to those skilled in the art. For example, such methods of preparation include chlorination of aluminum metal with chlorine, hydrogen chloride, and metal chlorides, i.e. lead chloride, copper chloride, and silver chloride. Aluminum chloride can also be prepared by the reaction of alumina and aluminiferous ores with chlorine, hydrogen chloride, metal chlorides and the like.

Anhydrous aluminum chloride is extremely hygroscopic and consequently caution should be taken to minimize the exposure of aluminum chloride to the air to avoid premature reaction of said aluminum chloride.

' Suitable solvents in which the reaction can be conducted include saturated aliphatic'hydrocarbons such as n-penethylcyclobutane, cyclopentane, methylcyclopentane, methylcyclohexane, cyclohexane and the like; halogenated aliphatic hydrocarbons such as ethyl chloride, ethyl bromide, ethyl iodide, n-propyl chloride, isopropyl chloride, butyl chloride, isobutyl chloride, propyl iodide, ethylene dichloride, methylene chloride, methylene bromide, chloroform, carbon tetrachloride and the like; aromatic hydrocarbons such as benzene, toluene, xylene, ethylbenzene, n-propylbenzene and the like; halogenated aromatic hydrocarbons such as chlorobenzene, dichlorobenzene, bromobenzene, dibromobenzene, iodobenzene, benzyl chloride, chlorotoluene, bromotoluene, iodotoluene and the .like; and nitro derivatives of aromatic hydrocarbons such as nitrobenzene and the like. In general, it i preferred to employ solvents in the process of this invention which are highly polar in nature and are inert under the conditions of the reaction. Those solvents which have a boiling point of up to about C. are particularly preferred for use in this invention.

Those skilled in the art will recognize that the process of this invention is not limited to specific reaction temperatures since said process can be carried out at temperatures of from 0 C. to temperatures of 105 C. or more. A reaction temperature of 0 C. can be maintained, for example, by employing a cooling bath comprising a slurry of ice in water and using methylene chloride or chloroform as a reaction solvent. As will be appreciated, the rate of reaction at temperatures 0 C. to 10 C. will be somewhat slow. The minimum temperature for the process of this invention is therefore the temperature just above that at which no reaction takes place between the alkyl o-hydroxyphenyl ether, tertiary amine and aluminum chloride.

Temperatures such as those greater than 105 C. can i also be used in the process of this invention. However, degradation results in considerable tar in the reaction product. At higher temperatures shorter reaction periods may be used to overcome the degradation problem. The yield of product falls off with the longer reaction time at higher temperatures, i.e. greater than 105 C. Temperatures within the range of from about 0 C. to about 55 C. can be most advantageously used, while temperatures within the range of from about 40 C. to 45 C. are especially preferred.

The tertiary amine, anhydrous aluminum chloride and ether employed in the practice of this invention can be used in ratios which vary over a rather wide range. For example, with each mole of the ether, from 1.4 to about 14.0 moles of the amine can be added. Similarly, with each mole of the ether, there can be added from 0.5 to about 3.5 mole of the aluminum chloride. It should be pointed out that a molar ratio of about 4.4:1.1 .:1.0 (aminezaluminum chloridezether) is particularly preferred.

The product of the ether-amine-aluminum chloride reaction is then hydrolyzed with an aqueous acid. Although a wide range of acids can be employed for such hydrolysis, it has been found that optimum yields are obtained with acids such as sulfuric, phosphoric, hydrochloric and the like.

After the reaction is complete, the product can be recovered by any method well known to those skilled in and efiicient separation of the reaction product and any unreacted alkyl o-hydroxyphenyl ether. For example, the reaction mixture is permitted to settle into two phases, i.e. an organic phase and an aqueous phase. It is generally found upon separation of the two phases that the aqueous phase contains in efiect all of the desired reaction product, and the organic phase contains all of the unreacted alkyl o-hydroxyphenyl ether. The aqueous phase is treated by a solvent extraction technique to isolate the desired product. Any unreacted components are recovered from the organic phase for reuse in the process by evaporation. As an alternative, the organic phase can be dried by azeotropic distillation and recycled to the process.

The invention .will be more fully understood by reference to the following examples. These examples, however, are given for the purpose of illustration only and are not to be construed as limiting the scope of the present invention in any way. v

Example I A suitable reaction vessel, designed to exclude atmospheric moisture, is equipped with agitation means, means for measuring the temperature of liquids and vapors, heating and cooling means, and means for condensing vapors. Said vessel is charged with 152 grams (1.0 mole) of vanillin and 1500 ml. of methylene chloride, and

' 146.8 grams (1.1 moles) of anhydrous aluminum chloride is suspended in the charged materials. 348.0 grams (4.4 moles) of pyridine is then added with agitation and cooling at such a rate as to maintain the reaction temperature at 3035 C. The resulting solution of the reaction complex in the solvent is heated to the reflux temperature of the solvent (44 C.) and maintained at said temperature for about 24 hours. Said solution is then cooled to C. and hydrolyzed with cooling by the addition of dilute (IS-20%) hydrochloric acid until the solution is acidic to a Congo red indicator. The aqueous phase and the methylene chloride phase are separated. The former is extracted with four 500 ml. portions of ether. The combined ether extracts are evaporated to obtain crystalline protocatechualdehyde in a yield of 87% of theory and having a M.P. 153l54 C.

The methylene chloride phase contains substantially all of the unreacted vanillin, Said vanillin may be recovered by evaporation. As an alternative, the methylene chloride phase can be dried by azeotropic distillation and recycled to the process.

Example 11 A reaction vessel as described in Example I is charged with 166 grams (1.0 mole) of acetovanillone and 1500 ml. of methylene chloride, and 146.8 grams 1.1 moles) of anhydrous aluminum chloride is suspended 'in the charged materials. 348.0 grams (4.4 moles) of pyridine is then added with agitation and cooling at such a rate as to maintain the reaction temperature at -35 C. The resulting solution of the reaction complex in the solvent is heated to the reflux temperature of the solvent (44 C) and maintained at said temperature for about 24 hours. Said solution is then cooled to 20 C. and hydrolyzed with cooling by the addition of dilute (15- 20%) hydrochloric acid until the solution is acidic to a Congo red indicator. The aqueous phase and the methylene chloride phase are separated. The former is extracted with four 500 ml. portions of ether. The combined ether extracts are evaporated to obtain crystalline 3,4-dihydroxyacetophenone in a yield of 70% of theory and having a M.P. 110-112" C.

The methylene chloride phase contains substantially all of the unreacted acetovanillone; Said acetovanillone may be recovered by evaporation. As an alternative, the methylene chloride phase can be dried by azeotropic distillation and recycled to the process.

Example III Following the procedure of Example I, 124 grams (1.0 mole) of guaiacol, 146.8 grams (1.1 moles) of anhydrous aluminum chloride, 1500 m1. of methylene chloride and 348.0 grams (4.4 moles) of pyridine are utilized to prepare catechol, M.P. 103105 C., in a yield of 78% of theory.

1 Example IV Following the procedure of Example I, 152 grams (1.0 mole) of isovanillin, 146.8 grams (1.1 moles) of anhydrous aluminum chloride, 1500 ml. of methylene chloride and 348 grams (4.4 moles) of pyridine are utilized to pre- 6 pare protocatechualdehyde, M.P. 153-154 C., in a yield of 88% of theory.

Examples V-IX Ether:4-hydroxy-3-methoxy ethylbenzyl alcohol Product=3,4-dihydroxy ethylbenzyl alcohol (VII) Ether=4-hydroxy-3-methoxy dimethylbenzyl alcohol Product=3,4-dihydroxy dimethylbenzyl alcohol 7 (VIII) Ether:1-(4-hydroxy-3-rnethoxyphenyl)-l-hydroxy-2- (Z-methoxyphenoxy propane Product: 1- 3 ,4-dihydroxyphenyl l-hydroxy-Z- (Z-meth-oxyphenoxy propane Ether=syringyl alcohol Product:3,4-dihydroxy-5-methoxybenzyl alcohol Example X A reaction vessel as described in Example I is charged with 152 grams (1.0 mole) of vanillin and 1500 ml. of chloroform, and 146.8 grams (1.1 moles) of anhydrous aluminum chloride is suspended in the charged materials. 348.0 grams (4.4 moles) of pyridine is then added with agitation and cooling at such a rate as to maintain the reaction temperature at 30-35 C. The resulting solution of the reaction complex in the solvent is heated to the reflux temperature of the solvent (66 C.) and maintained at said temperature for about 24 hours. Said solution is then cooled to 20 C. and hydrolyzed with cooling by the addition of dilute (1520%) hydrochloric acid until the solution is acidic to a Congo red indicator. The aqueous phase and the chloroform phase are separated. The former is extracted with four 500 ml. portions of ether. The combined ether extracts are evaporated to obtain crystalline protocatechualdehyde in a yield of 77% of theory and having a'M.P. 153154 C.

The chloroform phase contains substantially all of the unreacted vanillin. Said vanillin may be recovered by evaporation. As an alternative, the chloroform phase can be dried by azeotropic distillation and recycled to the process.

Example XI A reaction vessel as described in Example I is charged with 152 grams (1.0 mole) of vanillin and 1500 ml. of chloroform, and 146.8 grams (1.1 moles) of anhydrous aluminum chloride is suspended in the charged materials. 348.0 grams (4.4 moles) of pyridine is then added with agitation and cooling at such a rate as to maintain the reaction temperature at 30-35" C. The resulting solution of the reaction complex in the solvent is heated to a temperature of 45 C. and maintained at said temperature for about 24 hours. Said solution is then cooled to 20 C. and hydrolyzed with cooling by the addition of dilute (IS-20%) hydrochloric acid until the solution is acidic to a Congo red indicator. The aqueous phase and the chloroform phase are separated. The former is extracted with four 500 ml. portions of ether. The combined ether extracts are evaporated to obtain crystalline protocatechualdehyde in a yield of 76% of theory and having a M.P. 152153 C.

The chloroform phase contains substantially all of the unreacted vanillin. Said vanillin may be recovered by evaporation. As an alternative, the chloroform phase can be dried by azeotropic distillation and recycled to the process. I

Example XII A reaction vessel as described in Example I is charged with 152 grams (1.0 mole) of vanillin and 1500 ml. of ethyl bromide, and 146.8 grams (1.1 moles) of anhydrous aluminum chloride is suspended in the charged materials. 348.0 grams (4.4 moles) of pyridine is then added with agitation and cooling at such a rate as to maintain the reaction temperature at 3035 C. The resulting solution of the reaction complex in the solvent is heated to the reflux temperature of the solvent (40 C.) and maintained at said temperature for about 24 hours. Said solution is then cooled to 20 C. and hydrolyzed with cooling by the addition of dilute (IS-20%) hydrochloric acid until the solution is acidic to a Congo red indicator. The aqueous phase and the ethyl bromide phase are separated. The former is extracted with four 500 ml. portions of ether. The combined ether extracts are evaporated to obtain crystalline protocatechualdehyde in a yield of 87% of theory and having a M.P. l53l54 C.

The ethyl bromide phase contains substantially all of the unreacted vanillin. Said vanillin may be recovered by evaporation. As an alternative, the ethyl bromide phase can be dried by azeotropic distillation and recycled to the process.

' Example XIII Following the procedure of Example I, 182 grams (1.0 mole) of syringaldehyde, 146.8 grams (1.1 mole) of anhydrous aluminum chloride, 1500 ml. of methylene chloride and 348.0 grams (4.4 moles) of pyridine are utilized to prepare 3-methoxy-4,S-dihydroxybenzaldehyde, M.P. 131-l33 C., in a yield of 79% of theory.

Example XIV A reaction vessel as described in Example I is charged with 152 grams (1.0 mole) of vanillin and 1500 ml. of ethylene dichloride, and 146.8 (1.1 moles) of anhydrous aluminum chloride is suspended in the charged mate-rials. 348.0 gram (4.4 moles) of pyridine is then added With agitation and cooling at such a rate as to maintain the reaction temperature at 3035 C. The resulting solution of the reaction complex in the solvent is heated to a temperature of 45 C. and maintained at said temperature for about 24 hours. Said solution is then cooled to 20 C. and hydrolyzed with cooling by the addition of dilute (-20%) hydrochloric acid until the solution is acidic to a Congo red indicator. The aqueous phase and the ethylene dichloride phase are separated. The former is extracted with four 500 ml. portions of ether. The combined ether extracts are evaporated tdobtain crystalline protocatechualdehyde in a yield of 76% of theory and having a M.P. l49l51 C.

The ethylene dichloride phase contains substantially all of the unreacted vanillin. Said vanillin may be recovered by evaporation. As an alternative, the ethylene dichloride phase can be dried by azeotropic distillation and recycled to the process.

Example XV Following the procedure of Example I, 152 grams (1.0 mole) of vanillin, 146.8 grams (1.1 moles) of anhydrous aluminum chloride, 1500 ml. of methylene chloride, and 410 grams (4. 4 moles) of 'y-picoline are utilized to prepare protocatechualdehyde in a yield of 73% of theory.

Example XVI Following the procedure of Example 1,152 grams (1.0 mole) of vanillin, 146.8 grams (1.1. moles) of anhydrous aluminum chloride, 1500 ml. of methylene chloride, and

410 grams (4.4 moles) of a-picoline were utilized to. prepare protocatechualdehyde in a yield of 41% of theory.

Example XVII Following the procedure of Example I, 152 grams (1.0 mole) of vanillin, 146.8 grams (1.1 moles) of anhydrous aluminum chloride, 1500 ml. of methylene chloride, and 567 grams (4.4 moles) of quinoline are utilized to prepare protocatechualdeliyde in a yield of 23% of theory.

Example XVIII Following the procedure of Example I, 15 2 grams (1.0 mole) of vanillin, 146.8 grams 1.1 moles) of anhydrous aluminum chloride, 1500 ml. of methylene chloride, and 532 grams (4.4 moles) of N,N-dimethylaniline are utilized to prepare protocatechualdehyde in a yield of 33% of theory.

Example XIX A reaction vessel as described in Example I is charged with 166 grams (1.0 mole) of 3-ethoxy-4-hydroxybenzaldehyde and 1500 ml. of methylene chloride, and 146.8 grams (1.1 moles) of anhydrous aluminum chloride is suspended in the charged materials. 348.0 grams (4.4 moles) of pyridine is then added with agitation and cooling at such a rate as to maintain the reaction temperature at 3035 C. The resulting solution of the reaction complex in the solvent is heated to the reflux temperature of the solvent (44 C.) and maintained at said temperature ride phase can be dried by azeotropic distillation and recycled to the process.

Examples XX-XXIII Following the procedure of Example I, 1.0 mole of each of the alkyl o-hydroxyphenyl ethers tabulated below is substituted for the benzaldehyde. The product obtained in each instance is as indicated.

Ether li-hydroxyconiferyl alcohol Product: 3- 3 ,4-dihydroxyphenyl) -2-propenl ,2-diol (XXI) Ether:4-hydroxy-3-methoxybenzyl alcohol Product:3,4-dihydroxybenzyl alcohol (XXII) Ether:fl-hydroxypropionylguaiacone Product:2,3,4'-trihydroxypropiophenone (XXIII) Ether=coniferyl aldehyde Pro duct: 3,4-di-hydroxycinnamaldehyde Example XXIV Following the procedure of Example I, 168 grams (1.0 mole) of vanillic acid, 146.8 grams (1.1 moles) of-anhydrous aluminum chloride, 1500 ml. of methylene chloride, and 348 grams (4.4 moles) of pyridine are utilized to prepare protocatechuic acid in a yield of 28% of theory.

Example XXV Following the procedure of Example I, 152.0 grams (1.0 mole) of vanillin, 146.8 grams (1.1 moles) of an- 9 hydrous aluminum chloride, 1500 ml. of methylene chloride and 444 grams (4.4 moles) of triethylam-ine are utilized to prepare protocatechualdehyde, M.P. 152-154 C., in a yield of 62% of theory.

for cleaving alkyl -o-hydroxyphenyl ethers. The reaction conditions are mild, and a pure product is recovered with comparative ease.

While this invention has been described wlth respect Emm le YXVI to certain embodiments, it is not so limited, and it is to p I be understood that variations and modifications thereof Following the Procedure of Example 231 grams may be made which are obvious to those skilled in the' mole) of S-bromovanillin, 146.8 grams (1.1 moles) of art without departing from the spirit or scope of this inanhydrous aluminum chloride, 1500 ml. of methylene ti Chloride, and 348 grams molas) 0f Py are The embodiments of the invention in which an excluhzed to prepare 5-bromo-protocatechualdehyde, M.P. sive property or privilege is claimed are defined as fol- 225-227 (3., in a yield of 90% of theory. lows:

Example XXI/H 1. A process which comprises reacting an alkyl o-hyd roxyphenyl ether of formula Following the procedure of Example I, 164 grams (1.0 (RH) mole) of eugenol, 146.8 grams (1.1 moles) of anhydrous aluminum chloride, 1500 ml. of methylene chloride, and 348 grams (4.4 moles) ofpyridine are utilized to prepare 4-allyl catechol, M.P. 4850 C., in good yield.

Example XXVIII 5,,

Following the procedure of Example I, 197 grams (1.0 g mole) of Z-nitrovanillin, 146.8 grams (1.1 moles) of anwhere alkyl radical contammg from 1 to 4 l l atoms, R is a radical selected from the group consisting hydrous aluminum chloride, 1500 ml. of methylene chlop of hydrogen, halogen and alkyl, alkenyl and alkoxy rad1- ride, and 348 grams (4.4 moles) of pyridine are utilized to re are 2-nitro rotocatec hualde'h de in excellent ied Gals contammg from 1 to 4 carbon atoms R 15 a radlcal p p p y y 1 selected from the group consistingof halogen, nitro, sulple XXIX fomethyl, sulfinomethyl, meroaptomethyl, sulfenomethyl, Following the procedure of Example I, 153 grams (1.0 hydfoxyl and hydrocarbon and oxygelgated hyd'mcargon mole) of vanillyl amine, 146.8 grams (1.1 moles) of anl l contammg from to 18.car on atoms n hydrous aluminum chloride, 1500 ml. of methylene chlo- 15 an Integer from 0 Wlth a E l hydrocar'byl amme ride, and 348 grams (4.4 moles) of pyridine are utilized a anhydlfous lalummugl g f i of a inert organic so vent, an t ereater y *ro yzmg e pro to prepqre d1 ydroxybenzylamme m good ylel not of said reaction with aqueous acid, there being from Example XXX 37 about 1.4 to about 14.0 moles of tertiary hydrocarbyl Following the procedure f Example 1 3 grams 1 0 0 amine and from about 0.5 to about 3.5 moles of aluminum mole) of vanillyl sulfenic acid, 146.8 grams (1.1 moles) chlfmde P mole 9 etherof anhydrous aluminum chloride, 1500 ml. of methylene A P Q Whwh cornPrlses reacting an alkyl Y chloride, and 348 grams (4.4 moles) of pyridine are utidroxyphenyl ether of formula lized to prepare 3,4-dihydroxybenzyl sulfenic acid in a (R )1. high yield.

. Example XXXI Following the procedure of Example I, 170 grams (1.0 mole) of vanillyl mercaptan, 146.8 grams (1.1 moles) of anhydrous aluminum chloride, 1500 ml. of methylene B chloride, and 348 grams (4.4 moles) of pyridine are uti- 1 1 lized to prepare 3,4-dihydroxybenzyl mercaptan in good where R is an alkyl radical containing from 1 to 4 caryield. bon atoms, R is a radical selected from the group con- Example X XX II sisting of hydrogen, halogen and alkyl, a-lkenyl and alkoxy 90 radicals containing froml to 4 carbon atoms, R" is a Following the procedure of Example I, 218 grams (1.0 radical selected from the group consisting of halogen, mole) of 4-hydroxy-3-methoxytoluene-w-sulfonic acid, nitro, sulfomethyl, sulfinomethyl, mercaptomethyl, sul- 146.8 grams (1.1 moles) of anhydrous aluminum chlofenomethyl, hydroxyl and hydrocarbon and oxygenated ride, 1500 ml. of methylene chloride, and 348 grams (4.4 W hydrocarbon radicals containing from 1 to 18 carbon moles) of pyridine are utilized to prepare 3,4-dihydroxyatoms, and n is an integer from 0 to 3, with a heterotoluene-w-sulfonic acid in a high yield. cyclic tertiary hydrocarbyl amine and anhydrous alumi- The following table represents additional examples num chloride in the presence of an inert organic solvent, of the present invention, wherein the apparatus of Exand thereafter hydrolyzing the product of said reaction ample I is utilized, and the procedure and reactants emwith aqueous acid, there being from about 1.4 to about ployed are as specified. 60 14.0 moles of tertiary hydrocarbyl amine and from about TABLE I Example No. Molar Ratios Reaetants Solvent Reaction Reaction Percent PyridinezAlCls:Vanillin Temp, C. Time, hrs. Conversion XXXIII Hexane 68 1 34. 1 011013 0-10 48 16.8 CHCIL 25-30 24 38.5 014013 .4 25-30 24 66.7 CHCIQ 25-30 72 68.1 Orton 40 45 24 51.5 011013 -55 24 52.8 CHOh 50-55 24 37 OgHfiNO 25-30 24 33.8 one]; 40-45 24 73.4 XXXXIII 011015 40-45 24 75.1

From these exemplary preparations it will be seen that this invention provides a simple and inexpensive method 0.5 to about 3.5 moles of aluminum chloride per mole of ether.

3. The process of claim 2 wherein the heterocyclic tertiary hydrocarbyl amine is pyridine.

4. The process of claim 2 wherein the heterocyclic tertiary hydrocarbyl amine is y-picoline.

5. The process according to claim 2 wherein the inert organic solvent is methylene chloride.

6. A process which comprises reacting an alkyl o-hydroxyphenyl ether of formula where R is an alkyl radical containing from 1 to '4 carbon atoms, R is a radical selected from the group consisting of hydrogen, halogen and alkyl, alkenyl and alkoxy'radicals containing from 1 to 4 carbon atoms, R is a radical selected from the group consisting of halogen, nitro, sulfomethyl, sul-finomethyl, mercaptomethyl, sulfenomethyl, hydroxyl and hydrocarbon and oxygenated hydrocarbon radicals containing from 1 to 18 carbon atoms, and n is an integer from 0 to 3, with anhydrous aluminum chloride in the presence of an inert organic solvent and thereafter hydrolyzing the product of said reaction with an aqueous acid, there being from about 1.4 to about 14.0 moles of tertiary hydrocarbyl amine and from about 0.5 to about 3.5 moles of aluminum chloride per mole of guaiacol.

9. The process as defined in claim 8 wherein the tertiary hydrocarbyl amine is pyridine and the inert organic solvent is methylene chloride.

10. A process of preparing protocatechualdehyde which comprises reacting vanillin with a tertiary hydrocarbyl .amine and anhydrous aluminum chloride in the presence of an inert organic solvent and thereafter hydrolyzing the product of said reaction with an aqueous acid,

there being from about 1.4 to about 14.0 moles of tertiary hydrocarbyl amine and from about 0.5 to about 3.5 moles of aluminum chloride per mole of vanillin.

11. The process as defined in claim 10 wherein the tertiary hydrocarbyl amine is pyridine and the inert organic solvent is methylene chloride.

12. A process of preparing 3,4-dihydroxyacetophenone which comprises reacting acetovanillone with a tertiary hydrocarbyl amine and anhydrous aluminum chloride in the presence of an inert organic solvent and thereafter hydrolyzing the product of said reaction with an aqueous acid, there being from about 1.4 to about 14.0 moles of tertiary hydrocarbyl amine and from about 0.5 to about 3.5 moles of aluminum chloride per mole of acetovanillone.

13. The process as defined in claim 12 wherein the tertiary hydrocarbyl amine is pyridine and the inert organic solvent is methylene chloride.

14. A process of preparing 3,4-dihydroxy-5-methoxybenzaldehyde which comprises reacting syringaldehyde with a tertiary hydrocarbyl amine and anhydrous alu minum chloride in the presence of an inert organic solvent and thereafter hydrolyzing the product of said reaction with an aqueous acid, there being from about 1.4 to about 14.0 moles of tertiary hydrocarbyl amine and from about 0.5 to about 3.5 moles of aluminum chloride per mole of syringaldehyde.

15. The process as defined in claim '14 wherein the tertiary hydrocarbyl amine is pyridine and the inert organic solvent is methylene chloride.

16. A process of preparing S-bromoprotocatechualdehyde which comprises reacting S-bromovanillin with a tertiary hydrocanbyl amine and anhydrous aluminum chloride in the presence of an inert organic solvent and thereafter hydrolyzing the product of said reaction with an aqueous acid, there being from about 1.4 to about 14.0 moles of tertiary hydrocarbyl amine and from about 0.5 to about 3.5 moles of aluminum chloride per mole of 5-bromovanillin.

17. The process as defined in claim 16 wherein the tertiary hydrocarbyl amine is pyridine and the inert organic solvent is methylene chloride.

References Cited by the Examiner UNITED STATES PATENTS 11/1937 Tinker et al. 2606'21 3/1959 Kamlet 260-600 CHARLES B. PARKER, JOSEPH R. LIBERMAN,

Examiners. 

1. A PROCESS WHICH COMPRISES REACTING AN ALKYL O-HYDROXYPHENYL ETHER OF FORMULA 